The general objective of this project is to increase our understanding of the biology of carcinogenesis. Carcinogenesis is interpreted to mean the whole series of events and processes that result in a fully developed, metastasizing neoplasm. A major portion of the work is therefore concerned with the interactions of a neoplastically transformed cell or clone with the host. In particular, emphasis will be given to the investigation of the role of the immune response. In 1981 to 1982, nearly formal proof was obtained that oncogenesis is aided and abetted by a modest immune reaction, i.e., oncogenesis is facilitated by a low level of immune reaction. During the past year, preliminary evidence has suggested that the optimal level of host immune-capacity for oncogenesis is inversely related to the dose of oncogen. With very low doses, the normal host immune-capacity is less than optimal; with large doses, immunodepression, above that produced by the oncogen itself, is required for optimal oncogenesis. The immune reaction appears to be a regulator of oncogenesis rather than a purely defensive phenomenon. During the coming year, the mechanisms of the immunological stimulation of oncogenesis will be investigated. It is hoped that these studies will give insight into ways in which immunological stimulation of oncogenesis can be prevented and immunological surveillance made more effective. The work will also provide a better perspective of the role of the immune system in evolution and its functions in normal growth control and tissue homeostasis. (IP)